Obata T
Department of Pharmacology, Oita Medical University, Japan.
Eur J Pharmacol. 1999 Jul 28;378(1):39-45. doi: 10.1016/s0014-2999(99)00450-1.
We examined the antioxidant effects of angiotensin-converting enzyme inhibitor on 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (*OH) formation in extracellular fluid of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol microl(-1) min(-1) was infused through a microdialysis probe to detect the generation of *OH, as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP+ clearly produced an increase in *OH formation in a concentration-dependent manner. When imidaprilat was infused in MPP+ -pre-treated animals, the formation of dopamine and 2,3-DHBA significantly decreased, as compared with that in the MPP+ -only-treated group. We compared the ability of two non-SH-containing angiotensin-converting enzyme inhibitors (imidaprilat and enalaprilat) with an SH-containing angiotensin-converting enzyme inhibitor (captopril) to scavenge *OH. All three angiotensin-converting enzyme inhibitors were able to scavenge *OH generated by the action of MPP+. However, the changes produced by captopril and enalaprilat were not significant. When dopamine was administered to the MPP+ -pre-treatment group, a marked elevation was observed, showing a positive linear correlation between dopamine and *OH formation (2,3-DHBA) in the dialysate. Moreover, when iron (II) was administered to the MPP+ -pre-treatment group, the same results were obtained: a positive linear correlation (R2 = 0.989) between the release of dopamine and 2,3-DHBA (R2 = 0.989) in the dialysate. When corresponding experiments were performed with imidaprilat-pre-treated animals, the level of 2,3-DHBA decreased. These results suggested that angiotensin-converting enzyme inhibitors may protect against MPP+ -induced *OH formation in the rat striatum.
我们研究了血管紧张素转换酶抑制剂对1-甲基-4-苯基吡啶离子（MPP+）诱导的大鼠纹状体细胞外液中羟自由基（OH）形成的抗氧化作用。将大鼠麻醉后，通过微透析探针以林格氏溶液输注水杨酸钠（0.5 nmol μl-1 min-1）来检测OH的生成，这可通过纹状体中2,3-二羟基苯甲酸（DHBA）的非酶形成来反映。MPP+明显以浓度依赖性方式增加OH的形成。当对MPP+预处理的动物输注咪达普利拉时，与仅用MPP+处理的组相比，多巴胺和2,3-DHBA的形成显著减少。我们比较了两种不含巯基的血管紧张素转换酶抑制剂（咪达普利拉和依那普利拉）与一种含巯基的血管紧张素转换酶抑制剂（卡托普利）清除OH的能力。所有三种血管紧张素转换酶抑制剂均能够清除MPP+作用产生的OH。然而，卡托普利和依那普利拉产生的变化不显著。当对MPP+预处理组给予多巴胺时，观察到明显升高，表明透析液中多巴胺与OH形成（2,3-DHBA）之间呈正线性相关。此外，当对MPP+预处理组给予铁（II）时，得到相同结果：透析液中多巴胺释放与2,3-DHBA之间呈正线性相关（R2 = 0.989）。当对咪达普利拉预处理的动物进行相应实验时，2,3-DHBA水平降低。这些结果表明血管紧张素转换酶抑制剂可能对MPP+诱导的大鼠纹状体中*OH形成具有保护作用。
